In the process of examining the possible neurobiological mechanisms underlying alcoholism, it has been suggested that the formation of aberrant amine metabolite3s, tetrahydroisoquinolines (TIQs), might be responsible for some of the effects of alcohol. Although these compounds have been investigated for their influence on neurochemical parameters and interactions with some of the effects of ethanol, their role in tolerance to ethanol has not yet been examined. Tolerance to ethanol is a many-faceted phenomenon important in the development of the biomedical problems of alcoholism. Several different types of tolerance have been defined: acute, enfironment-dependent, environment-independent and metobolic/dispositional. The use of neurotoxins to selectively destroy either the central noradrenergic or serotonergic systems has demonstrated the importance of these systems in environment-dependent and environment-independent tolerance. Certain TIQs have been shown to interact with these neurotransmitter systems, and to have long-term effects. Therefore, one set of TIQs, which have been found to be present in vivo and to interact with these systems, will be tested for their effects on each type of tolerance.